Free secretory component from cystic fibrosis sputa displays the cystic fibrosis glycosylation phenotype

Lindsay J. Marshall, Beatrice Perks, Kathleen Bodey, Ranjan Suri, Andrew Bush, Janis K. Shute

Research output: Contribution to journalArticle

Abstract

Secretory IgA contributes to humoral defense mechanisms against pathogens targeting mucosal surfaces, and secretory component (SC) fulfills multiple roles in this defense. The aims of this study were to quantify total SC and to analyze the form of free SC in sputa from normal subjects, subjects with asthma, and subjects with cystic fibrosis (CF). Significantly higher levels of SC were detected in CF compared with both other groups. Gel filtration chromatography revealed that SC in CF was relatively degraded. Free SC normally binds interleukin (IL)-8 and inhibits its function. However, in CF sputa, IL-8 binding to intact SC was reduced. Analysis of the total carbohydrate content of free SC signified overglycosylation in CF compared with normal subjects and subjects with asthma. Monosaccharide composition analysis of free SC from CF subjects revealed overfucosylation and undersialylation, in agreement with the reported CF glycosylation phenotype. SC binding to IL-8 did not interfere with the binding of IL-8 to heparin, indicating distinct binding sites on IL-8 for negative regulation of function by SC and heparin. We suggest that defective structure and function of SC contribute to the characteristic sustained inflammatory response in the CF airways.
Original languageEnglish
Pages (from-to)399-406
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume169
Issue number3
Early online date3 Nov 2003
DOIs
Publication statusPublished - Feb 2004

Keywords

  • polymeric immunoglobulin receptor
  • glycoproteins,
  • inflammation
  • respiratory mucosa

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